Natural antimicrobial polymeric coatings for contamination resistant wound dressings: biocompatibility and in vivo efficacy against MRSA.

The growing threat of antimicrobial resistance and complications from chronic wound infections have amplified the demand for natural, bioactive wound care solutions that can both prevent infection and modulate inflammation. Although there are different antimicrobial coating solutions, their incorporation into complex medical devices is challenging. Here, we demonstrate the successful translation of poly-L-arginine (PAR) and hyaluronic acid (HA) antimicrobial coatings into fully assembled multilayer wound dressing prototypes, enabling evaluation under clinically relevant conditions that closely mimic commercial superabsorbent dressings. To demonstrate its efficacy, in this study, we evaluated and compared three wound dressing prototypes: (i) the unmodified multilayer absorbent dressing, (ii) a prototype featuring a bioactive coating composed of alternating layers of PAR and HA applied to the wound contact layer, and (iii) the same coated version covered with a perforated silicone barrier layer. Antibacterial assays on the coated wound contact layers confirmed potent in vitro activity, achieving complete eradication of bacterial colonies compared to uncoated controls. To assess the safety, we first conducted in vitro cytotoxicity tests using Balb 3T3 mouse fibroblast cells, demonstrating that the PAR/HA coating was non-cytotoxic and well tolerated by mammalian cells. We then evaluated the in vivo antimicrobial efficacy and employed a murine wound model infected with methicillin-resistant Staphylococcus aureus (MRSA). The coated wound dressing significantly reduced bacterial burden in the wound bed, achieving a 5.39-log reduction compared to the un-coated control. The silicone-covered prototype also showed a moderate but significant antimicrobial effect (1.69-log reduction). Bioluminescence imaging and CFU analysis confirmed the efficacy of both dressings, with minimal bacterial attachment to the wound contact layer (WCL). The coatings did not interfere with the exudate extraction, wound contact control and wound protection functions of the full prototypes. These findings demonstrate that the bioactive coating effectively limits bacterial proliferation and dampens biofilm formation, with the coated dressing showing the most potent effects. This work supports the therapeutic potential of antimicrobial, self-assembling biopolymer coated dressings as a prophylactic strategy to prevent biofilm-associated infections and excessive immune activation in acute wound settings.